rs755291566
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_144672.4(OTOA):āc.1727T>Cā(p.Ile576Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I576M) has been classified as Uncertain significance.
Frequency
Consequence
NM_144672.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOA | NM_144672.4 | c.1727T>C | p.Ile576Thr | missense_variant | 17/29 | ENST00000646100.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOA | ENST00000646100.2 | c.1727T>C | p.Ile576Thr | missense_variant | 17/29 | NM_144672.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251450Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135910
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 22AN XY: 727244
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 26, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 22, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 576 of the OTOA protein (p.Ile576Thr). This variant is present in population databases (rs755291566, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with OTOA-related conditions. ClinVar contains an entry for this variant (Variation ID: 521781). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at